Virus mimics human protein to capture cell growth machinery

Health

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Published: Friday, May 9, 2008, 11:12 [IST]

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Washington, May 9 : Researchers from the University of Wisconsin-Madison and Harvard Medical School have shed light on the deceptive nature viruses by finding that the human cytomegalovirus (HCMV) can mimic a common regulatory protein to seize normal cell growth machinery, upsetting a cell's primary anti-cancer mechanism.

The team reports that a viral protein, called UL97, masquerades as a normal regulatory enzyme to alter a tumour-suppressing protein in human cells.

Unlike the normal enzyme, which can be switched on and off by the cell as needed, the viral stand-in lacks an off switch and evades cellular control. The findings represent a previously unknown way that viruses can cause uncontrolled cell growth and division.

Cells normally have tight regulatory mechanisms in place to limit multiplication to appropriate situations, such as replacing worn-out cells or repairing damage. Uncontrolled cell proliferation can lead to cancer and other disorders.

One of the most important cellular control mechanisms works through a protein called the retinoblastoma tumour suppressor protein, which slows cell growth.

"The retinoblastoma pathway is like the brakes on a car. It prevents tumour cells from growing out of control," said Robert Kalejta, an assistant professor in the UW-Madison Institute for Molecular Virology and McArdle Laboratory for Cancer Research, who led the new study.

"This pathway is mutated in essentially all human cancers," he added.

Disrupting this pathway is also advantageous for viruses. Unable to reproduce on their own, viruses rely on co-opting their host's cellular machinery, like an occupying army taking over a local factory. They are especially good at overriding or bypassing built-in control mechanisms, Kalejta says.

"Viruses are well known to encode proteins that have similar activities to cellular proteins, but they're just different enough that they're beneficial to the virus," he said. [UL97] shares the same activities as the cellular protein, but it lacks all of the control mechanisms," he added.

In essence, UL97 disables the brakes and hits the gas. Once a host cell is primed toward growth, HCMV takes over and steals the cell's machinery to reproduce itself.

The virus's bloodhound-like ability to seek out and target the most essential pieces of a cell's machinery makes it a valuable research tool, Kalejta says.

Kalejta next hopes to use UL97 to find other proteins that may be important for cell growth. He also sees potential clinical applications down the road.

HCMV infection is very common and, though it remains asymptomatic in most people, it has been implicated in some cancers and can cause trouble in people with compromised or suppressed immune systems, such as AIDS patients and transplant recipients. In addition, UL97-like proteins are also found in the other seven human herpes viruses, some of which are directly linked to cancers.

The advantages of the research are two-fold, Kalejta said.

"We're studying a virus that causes human disease and might eventually find a way to treat that infection and help patients. At the same time, we're learning about how the cell works, which has implications for patients that don't have infections," he said.